Phosphorylated Groucho delays differentiation in the follicle stem cell lineage by providing a molecular memory of EGFR signaling in the niche
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE144167 | GEO | 2020/01/24
REPOSITORIES: GEO
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Project description: Not available
| S-EPMC5201033 | biostudies-literature
Project description:Phosphorylated Groucho delays differentiation in the follicle stem cell lineage by providing a molecular memory of EGFR signaling in the niche
| PRJNA602923 | ENA
Project description:Controlled signaling activity is vital for normal tissue homeostasis and oncogenic signaling activation facilitates tumorigenesis. Here we combine single-cell transcriptomics with in-depth genetic and imaging analysis to investigate the role of the EGFR-Ras and Hedgehog signaling pathways in homeostasis of the Drosophila follicle stem cell lineage. We find that Hedgehog signaling simultaneously promotes an undifferentiated state and induces differentiation via activation of the epithelial-mesenchymal-transition associated transcription factor Zfh1. Overactivation of Hedgehog signaling generates a mixed transcriptional state comparable to partial epithelial-mesenchymal-transition. EGFR-Ras overactivation induces cell cycle defects by activating the transcription factors Pointed and E2f1 and impedes differentiation. Overactivation of both pathways blocks differentiation and induces tumor-like growth where follicle cells exhibit a loss of tissue architecture, sustained proliferation and a reduced lifespan of the host. These findings provide new insight into how signaling pathways converge at the transcriptional level to prevent malignant cell behavior.
2026-02-18 | GSE290241 | GEO
Project description:Controlled signaling activity is vital for normal tissue homeostasis and oncogenic signaling activation facilitates tumorigenesis. Here we combine single-cell transcriptomics with in-depth genetic and imaging analysis to investigate the role of the EGFR-Ras and Hedgehog signaling pathways in homeostasis of the Drosophila follicle stem cell lineage. We find that Hedgehog signaling simultaneously promotes an undifferentiated state and induces differentiation via activation of the epithelial-mesenchymal-transition associated transcription factor Zfh1. Overactivation of Hedgehog signaling generates a mixed transcriptional state comparable to partial epithelial-mesenchymal-transition. EGFR-Ras overactivation induces cell cycle defects by activating the transcription factors Pointed and E2f1 and impedes differentiation. Overactivation of both pathways blocks differentiation and induces tumor-like growth where follicle cells exhibit a loss of tissue architecture, sustained proliferation and a reduced lifespan of the host. These findings provide new insight into how signaling pathways converge at the transcriptional level to prevent malignant cell behavior.
2026-02-18 | GSE291056 | GEO
Project description:Primordial follicle assembly is a process that occurs in the embryonic or early post natal ovary in which oocyte nests break down to form individual primordial follicles. The size of this initial pool of primordial follicles in part determines the reproductive lifespan of the female. Connective tissue growth factor (CTGF) was identified as a potential regulatory candidate for this process in a previous microarray analysis of follicle development. The current study examines the effects of CTGF and associated transforming growth factor beta 1 (TGFbeta-1) on follicle assembly. Ovaries were removed from newborn rat pups and placed in an organ culture system for two days to measure the effect of these factors on follicle assembly. In addition, ovaries were cultured and treated for ten days to determine the potential of CTGF and TGFbeta-1 to manipulate the primordial follicle pool size over a longer developmental time period. The ovaries treated with CTGF for two days were found to have an increased proportion of assembled follicles. TGFbeta-1 had no effect on primordial follicle assembly and in combination with CTGF decreased oocyte number in the ovary after two days of culture. Over ten days of treatment only the combined treatment of CTGF and TGFbeta-1 was found to cause an increase in the proportion of assembled follicles. Interestingly, treatment with TGFbeta-1 alone resulted in fewer total oocytes in the ovary and decreased the primordial follicle pool size after ten days of culture. Observations indicate that CTGF alone or in combination with TGFbeta-1 stimulates primordial follicle assembly and TGFbeta-1 can decrease the primordial follicle pool size. CTGF was found to regulate the ovarian transcriptome during primordial follicle assembly and an integrative network of genes was identified. CTGF is one of the first growth factors shown to promote primordial follicle assembly, while TGFbeta-1 is one of the first factors shown to decrease the primordial follicle pool size. These observations suggest the possibility of manipulating primordial follicle pool size and influencing female reproductive lifespan. We used microarrays to determine genes expressed differentially between control and CTGF (connective tissue growth factor) treated P0 ovary RNA samples from 3 control groups are compared to 3 CTGF treated ovary groups
2010-09-16 | E-GEOD-22096 | biostudies-arrayexpress
Project description:The ovary is one of the first organs to lose functionality with age. We found that aging of the Drosophila ovary is characterized by an accumulation of phenotypes in the somatic compartment, including failure of the follicle cells to encapsulate germ-cell cysts, an extended S phase, and increased DNA damage. In aged ovaries, follicle encapsulation defects are associated with the lack of a germ-cell cyst checkpoint in early oogenesis. Single-cell RNA sequencing revealed that, across all cell types in the ovary, cells in the follicle lineage have the highest number of differentially expressed genes. Overexpression of Atg8a, a key autophagy machinery gene homologous to mammalian LC3, specifically in follicle cells prevents age-associated decline in the follicle epithelium and loss of reproductive capacity. Collectively, these findings demonstrate that genetic manipulation of a small population of ovarian somatic cells is sufficient to improve both cell-autonomous and non-autonomous features of reproductive aging.
2026-04-06 | GSE318563 | GEO
Project description:Primordial follicle assembly is a process that occurs in the embryonic or early post natal ovary in which oocyte nests break down to form individual primordial follicles. The size of this initial pool of primordial follicles in part determines the reproductive lifespan of the female. Connective tissue growth factor (CTGF) was identified as a potential regulatory candidate for this process in a previous microarray analysis of follicle development. The current study examines the effects of CTGF and associated transforming growth factor beta 1 (TGFbeta-1) on follicle assembly. Ovaries were removed from newborn rat pups and placed in an organ culture system for two days to measure the effect of these factors on follicle assembly. In addition, ovaries were cultured and treated for ten days to determine the potential of CTGF and TGFbeta-1 to manipulate the primordial follicle pool size over a longer developmental time period. The ovaries treated with CTGF for two days were found to have an increased proportion of assembled follicles. TGFbeta-1 had no effect on primordial follicle assembly and in combination with CTGF decreased oocyte number in the ovary after two days of culture. Over ten days of treatment only the combined treatment of CTGF and TGFbeta-1 was found to cause an increase in the proportion of assembled follicles. Interestingly, treatment with TGFbeta-1 alone resulted in fewer total oocytes in the ovary and decreased the primordial follicle pool size after ten days of culture. Observations indicate that CTGF alone or in combination with TGFbeta-1 stimulates primordial follicle assembly and TGFbeta-1 can decrease the primordial follicle pool size. CTGF was found to regulate the ovarian transcriptome during primordial follicle assembly and an integrative network of genes was identified. CTGF is one of the first growth factors shown to promote primordial follicle assembly, while TGFbeta-1 is one of the first factors shown to decrease the primordial follicle pool size. These observations suggest the possibility of manipulating primordial follicle pool size and influencing female reproductive lifespan. We used microarrays to determine genes expressed differentially between control and CTGF (connective tissue growth factor) treated P0 ovary
2010-09-16 | GSE22096 | GEO
Project description:Bioactive sphingolipids serve as an essential building block of membranes, forming a selective barrier ensuring subcellular compartmentalization and facilitating cell type-specific intercellular communication through regulation of the plasma membrane receptor repertoire. How the cell type-specific lipid compositions are achieved and what is their functional significance in tissue morphogenesis and maintenance has remained unclear. Here, we identify a stem-cell specific role for ceramide synthase 4 (CerS4) in orchestrating fate decisions in the skin epidermis. Deletion of CerS4 in the epidermis prevents the effective establishment of the adult hair follicle bulge stem cell (HFSCs) niche due to altered differentiation trajectories of HFSC precursors towards upper hair follicle and inner bulge fates. Mechanistically, the HFSC differentiation defects arise from a stem cell intrinsic imbalance of key ceramides and sphingolipids, and associated hyperactivity of canonical Wnt signaling. The lack of HFSCs leads to disruption of hair follicle architecture and hair follicle barrier function, ultimately triggering a Th2-dominated immune infiltration closely resembling human atopic dermatitis. This work uncovers a fundamental role for a cell state-specific sphingolipid profile in epidermal stem cell homeostasis and the role of an intact stem cell niche in maintaining an intact skin barrier.
2025-01-23 | PXD047573 | Pride
Project description:Ovarian follicle selection plays an important role in the reproduction of sexually mature hens, and this process can directly affect the growth and development of follicles until the final ovulation, thus affecting laying performance and fecundity of hens. In the laying hen ovary, one follicle from a cohort of 8-13 follicles of 6-8 mm in diameter is selected daily to enter the preovulatory hierarchy. In this study, we globally compared the proteomes of chicken ovarian follicles before and after follicle selection. A total of 5883 proteins were identified in the proteomes of chicken 6-8 mm prehierarchical follicles and 12-15 mm hierarchical follicles. 259 proteins are differentially expressed in 12-15 mm hierarchical follicle compared with prehierarchical follicle, of which 175 proteins are up-regulated and 84 proteins are down-regulated. The Gene Ontology enrichment of differentially expressed proteins revealed enriched GO terms for peptidase activity, acrosin binding for their molecular function and in the process of negative regulation of peptidase activity, and regulation of fertilization. The KEGG pathway analysis indicated that differentially expressed proteins were enriched for ribosome, lysine degradation, and endocytosis pathways. Nine differentially expressed proteins including vitellogenin-1 were validated with Parallel Reaction Monitoring (PRM) analysis, and their functions were discussed. This study provided a global proteomic view of the development of chicken ovarian follicles, which will serve as a foundation for understanding the molecular signatures and pathways of follicle selection in hens.
2021-09-08 | PXD011470 | Pride
Project description:The hair follicle stem cell niche is an immune-privileged microenvironment, characterized by reduced antigen presentation, thus shielding against permanent immune-mediated tissue damage. In this study, we demonstrated the protective role of hair follicle-specific epidermal growth factor receptor (EGFR) against scarring hair follicle destruction. Mechanistically, disruption of EGFR signalling generated a cell-intrinsic hypersensitivity within the JAK-STAT1 pathway, which, synergistically with interferon gamma expressing CD8 T-cell and NK-cell-mediated inflammation, compromised the stem cell niche. Hair follicle-specific genetic depletion of either JAK1/2 or STAT1 or therapeutic inhibition of JAK1/2 ameliorated the inflammation, restored skin barrier function and activated the residual stem cells to resume hair growth in mouse models of epidermal and hair follicle-specific EGFR deletion. Skin biopsies from EGFR inhibitor-treated and cicatricial alopecia patients indicated active STAT1 signalling and interferon target expression. Notably, a case study of folliculitis decalvans, characterized by progressive hair loss, scaling and perifollicular erythema, demonstrated successful treatment with JAK1/2 inhibition. Our findings offer molecular insights and present a mechanism-based therapeutic strategy for addressing chronic folliculitis associated with EGFR-inhibitor anti-cancer therapy and cicatricial alopecia.
2024-07-31 | GSE273572 | GEO